Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor

Immunity. 1999 Aug;11(2):141-51. doi: 10.1016/s1074-7613(00)80089-8.


PD-1, a 55 kDa transmembrane protein containing an immunoreceptor tyrosine-based inhibitory motif, is induced in lymphocytes and monocytic cells following activation. Aged C57BL/6(B6)-PD-1(-/-) congenic mice spontaneously developed characteristic lupus-like proliferative arthritis and glomerulonephritis with predominant IgG3 deposition, which were markedly accelerated by introduction of a Fas mutation (lpr). Introduction of a PD-1 null mutation into the 2C-TCR (anti-H-2Ld) transgenic mice of the H-2(b/d) background resulted in the chronic and systemic graft-versus-host-like disease. Furthermore, CD8+ 2C-TCR+ PD-1(-/-) T cells exhibited markedly augmented proliferation in vitro in response to H-2d allogenic cells. Collectively, it is suggested that PD-1 is involved in the maintenance of peripheral self-tolerance by serving as a negative regulator of immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface*
  • Apoptosis Regulatory Proteins
  • Arthritis, Rheumatoid / etiology*
  • Genetic Linkage
  • H-2 Antigens / genetics
  • Immune Tolerance
  • Lupus Nephritis / etiology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred MRL lpr
  • Mice, Transgenic
  • Programmed Cell Death 1 Receptor
  • Proteins / genetics
  • Proteins / physiology*
  • T-Lymphocytes / immunology


  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • H-2 Antigens
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Proteins